Establishment of Neurotoxicity Assessment Using Microelectrode Array (MEA) with hiPSC-Derived Neurons and Evaluation of New Psychoactive Substances (NPS)

Background and Objectives@#Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. @*Methods@#and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. @*Conclusions@#Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

Surgical removal of a telemetry system in a cynomolgus monkey (Macaca fascicularis):a 12-month observation study / 한국실험동물학회지

Background@#Telemetry is a wireless implanted device that measures biological signals in conscious animals and usually requires surgery for its removal when the study is finished. After removing the device, the animals are either used for other studies or euthanatized.Case presentation: Herein, we report the case of a living cynomolgus monkey (Macaca fascicularis) that was used for the entire experimental period, instead of euthanasia, after surgical removal of an implanted telemetry system.Radiography was used to determine the status of the implanted telemetry, following which, a repair surgery was performed for removing the system; clinical signs were used to preserve the life of the cynomolgus monkey. Postoperative clinical signs, food consumption, hematology, and serum biochemistry were examined during the 12-month observational period. No abnormal readings or conditions were observed in the subject after implant removal. @*Conclusions@#This study may be a useful case report for living cynomolgus monkeys in telemetry implantations used throughout the study period. We suggest minimizing the suffering and improving the welfare of these animals.

Ca2+ Entry is Required for Mechanical Stimulation-induced ATP Release from Astrocyte

Astrocytes and neurons are inseparable partners in the brain. Neurotransmitters released from neurons activate corresponding G protein-coupled receptors (GPCR) expressed in astrocytes, resulting in release of gliotransmitters such as glutamate, D-serine, and ATP. These gliotransmitters in turn influence neuronal excitability and synaptic activities. Among these gliotransmitters, ATP regulates the level of network excitability and is critically involved in sleep homeostasis and astrocytic Ca2+ oscillations. ATP is known to be released from astrocytes by Ca2+-dependent manner. However, the precise source of Ca2+, whether it is Ca2+ entry from outside of cell or from the intracellular store, is still not clear yet. Here, we performed sniffer patch to detect ATP release from astrocyte by using various stimulation. We found that ATP was not released from astrocyte when Ca2+ was released from intracellular stores by activation of Galpha(q)-coupled GPCR including PAR1, P2YR, and B2R. More importantly, mechanical stimulation (MS)-induced ATP release from astrocyte was eliminated when external Ca2+ was omitted. Our results suggest that Ca2+ entry, but not release from intracellular Ca2+ store, is critical for MS-induced ATP release from astrocyte.

Clinical Observations of Inguinal hernia in Pediatric Patients

This article consists of a clinical analysis of 221 cases of the Pediatric Inguinal Hernia treated in General Surgery of Pusan Adventist Hospital, from January 1990 to June 1996. The results were as follows ; 1) Patients with inguinal hernia were 37.5% of total operative patients in the division of pediatric surgery 2) Males predominated over females by the ratio of 5.5:1 3) Of 221 cases, 101(54%) were on the Rt side, 80(43.1%) on the Lt side and the remainder (6.4%) on both side in case of Male. 20(58.8%) were on the Rt side, 13(38.2%) on the Lt sid and the remainder (3.0%) on both side in case of Female. 4) The chief Complaints were inguinal protrusion in 131 cases(59.3%) and scrotal enlargement in 77 cases(34.9%) 5) Peak incidence age (32 Months) & Duration of history (20.2 Months) 6) Associated diseases were found in 10 cases(4.9%) and they were cryptorchidism (1.47%), hydroclele (0.98%), Umbilical hermia (0.49%), Heart anomaly (0.49%), cleft palate (0.49%), Teratoma (0.49%), and Jejunal atresia (0.49%). Family History was denied. 7) All were indirect hernia. 8) Incarcerated cases were 6(2.7%) and the ratio of male to female was 2:1, and the location of incarcerated hernia was Rt (66.6%), and Lt (33.3%) 9) There were 70 cases of strangulation. 10) Intraperitoneal organ in hernial sac was noted in 5 cases (2.26%), and they were ovary and fallopian tube in 3 cases (1.35%), small intestine in 1 case (0.45%), cecum and appendix in 1 case (0.45%). 11) 215 (97%) of all hernia were repaired only by highligation of sac and 6(3%) were inforced with Bassini's posterior wall repair. 12) Mean postoperative hospitalization were 5.2 days. 13) Postoperative complications occured in only 2 cases : hematoma and edema 1, wound infection 1.

A Clinical Analysis of Intussusception in Infants and Children

This article consists of a clinical analysis of 171 cases of intussusception treated at the Department of General Surgery and Pediatrics of Pusan Adventist Hospital, during a five year period from Jan. 1991 to Dec. 1995. The results were as follows ; 1) On the age and sex distribution, the age incidence under 1 year old was the most common(73.1%), and male to female ratio was 1.48 : 1. 2) The seasonal variation was Autumn(35.1%), Spring(32.1%), Summer(19.9%), and Winter(12.9%). 3) On the hematologic laboratory finding, 68% were revealed leukocytosis above 10,000/mm3 in serum. 4) In etiology, idiopathic type was common(98.5%), and Meckel's diverticulum was rare(1.5%). 5) The frequent Symptoms and signs were abdominal pain and irritability(84.2%), bloody stool(83.6%), vomiting(80.7%), palpable abdominal mass(48.5%). 6) On comparison of barium reduction to methods of the operation in relation to duration of symptoms, within 12 hours was 81.4% : 15.7% and above 24 hours was 49% : 51% 7) The common anatomical type of intussusception was ileo-colic type (36.9%), and the common types of bowel resection were ileoileo type and ileoileocolic type(80%). 8) The methods of the operation were manual reduction(53.8%), bowel resection(30.8%), and spontaneous reduction(15.4%). 9) Postoperative complications occurred in 10 cases ; febrile convulsion 3 cases, wound infection 2 cases, and wound dehiscence, intestinal obstruction, pulmonary complication each 1 case. 10) The overall recurrence rate was 5.3% (8 cases); 6.6% (7 cases) were after barium reduction, and 1.5% (1 case) was after manual reduction.